A series of interesting molecules on the surfaces of cells will trigger the rejection of grafts of various kinds. Individuals will not accept the transplantation of tissues which differ from their own tissues in the identity of these molecules. Two classes of such molecules are the classical transplantation antigens and the tumor specific antigens. Preliminary amino acid sequence information on the H-2K and H-2D transplantation antigens of the mouse and their human counterparts has left a number of key questions unanswered regarding the origin, function, and evolutionary interrelationships of these molecules. We wish to identify evolutionary precursors or successors of these molecules and determine whether the molecules possess obvious functional regions such as the hypervariable and conserved regions of immunoglobulin molecules. We wish to known when the mouse transplantation antigens diverged from one another and from their human counterparts. The tumor specific antigens are molecules which will trigger the spontaneous rejection of tumor grafts from syngeneic donors. Each tumor possesses unique antigen(s) in the system we are studying, but the antigens appear to be lacking or only weakly antigenic in the cancers which are normally clinically observed. We wish to determine whether the antigens from various tumors are members of an evolutionarily homologous class of molecules, how they differ from each other, and whether any or all of them are related to any known class of normal or fetal cell surface molecules. The above questions will be approached through the microsequence analysis of the molecules using exciting new instrument systems now operational in our laboratories. We propose to obtain complete amino acid sequences of the H-2K and H-2D gene products and partial amino acid sequences of at least three tumor specific antigens.